Length-independent telomere damage drives post-mitotic cardiomyocyte senescence.

ABSTRACT: Ageing is the biggest risk factor for cardiovascular disease. Cellular senescence, a process driven in part by telomere shortening, has been implicated in age-related tissue dysfunction. Here, we address the question of how senescence is induced in rarely dividing/post-mitotic cardiomyocytes and investigate whether clearance of senescent cells attenuates age-related cardiac dysfunction. During ageing, human and murine cardiomyocytes acquire a senescent-like phenotype characterised by persistent DNA damage at telomere regions that can be driven by mitochondrial dysfunction and crucially can occur independently of cell division and telomere length. Length-independent telomere damage in cardiomyocytes activates the classical senescence-inducing pathways, p21^CIP and p16^INK4a

SUBMITTER: Anderson R 

PROVIDER: S-EPMC6396144 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature